Cytochrome P-450 is the terminal oxidase of the liver microsomal monoxygenase system which catalyzes the biotransformation of steroid hormones, drugs, carcinogens, and other environmental chemicals. This project is proposed to study the molecular organization, catalysis and the mechanism of carcinogen activation of this enzyme system. Specific goals are: (a). To further characterize the interactions between cytochrome P0450 and microsomal membrane. (b) To understand the effects of phospholipids on the catalytic activities of the monoxygenase system. (c) To elucidate the mechanisms of monoxygenase reactions with respect to the interactions between substrates and cytochrome P-450, the role of hydrogen peroxide, and the action of some inhibitors. (d) To further assess the relative importance of nuclear envelope and microsomes as sites of carcinogen activation. Other carcinogens such as N-acetyl-aminofluorene, carbon tetrachloride, and aflatoxin B1, will also be used. The nature and the possible specificities of the target macromolecules will be investigated. BIBLIOGRAPHIC REFERENCES: Yang, C.S. (1976). Studies on the Microsomal Aryl Hydrocarbon Hydroxylase. Fed. Proc. 36, Abstract 333. Yang,C.S. Interactions of Cytochrome P-450 with NADPH-Cytochrome P-450 Reductase in Microsomal Membrane. In the 3rd International Symposium on Microsomes and Drug Oxidation, July 21-24, 1976, Berlin.